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http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiolo
gy/acute-myocardial-infarction/

Acute Myocardial Infarction

H. Michael Bolooki
Arman Askari
Published: August 2010

Contents

Definition and etiology

Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Myocardial
infarction occurs when myocardial ischemia, a diminished blood supply to the heart, exceeds a critical threshold
and overwhelms myocardial cellular repair mechanisms designed to maintain normal operating function and
homeostasis. Ischemia at this critical threshold level for an extended period results in irreversible myocardial cell
damage or death.
Critical myocardial ischemia can occur as a result of increased myocardial metabolic demand, decreased
delivery of oxygen and nutrients to the myocardium via the coronary circulation, or both. An interruption in the
supply of myocardial oxygen and nutrients occurs when a thrombus is superimposed on an ulcerated or unstable
atherosclerotic plaque and results in coronary occlusion.1 A high-grade (>75%) fixed coronary artery stenosis
caused by atherosclerosis or a dynamic stenosis associated with coronary vasospasm can also limit the supply
of oxygen and nutrients and precipitate an MI. Conditions associated with increased myocardial metabolic
demand include extremes of physical exertion, severe hypertension (including forms of hypertrophic obstructive
cardiomyopathy), and severe aortic valve stenosis. Other cardiac valvular pathologies and low cardiac output
states associated with a decreased mean aortic pressure, which is the prime component of coronary perfusion
pressure, can also precipitate MI.
Myocardial infarction can be subcategorized on the basis of anatomic, morphologic, and diagnostic clinical
information. From an anatomic or morphologic standpoint, the two types of MI are transmural and nontransmural.
A transmural MI is characterized by ischemic necrosis of the full thickness of the affected muscle segment(s),
extending from the endocardium through the myocardium to the epicardium. A nontransmural MI is defined as an
area of ischemic necrosis that does not extend through the full thickness of myocardial wall segment(s). In a
nontransmural MI, the area of ischemic necrosis is limited to the endocardium or to the endocardium and
myocardium. It is the endocardial and subendocardial zones of the myocardial wall segment that are the least
perfused regions of the heart and the most vulnerable to conditions of ischemia. An older subclassification of MI,
based on clinical diagnostic criteria, is determined by the presence or absence of Q waves on an
electrocardiogram (ECG). However, the presence or absence of Q waves does not distinguish a transmural from
a nontransmural MI as determined by pathology.2

A consensus statement was published to give a universal definition of the term myocardial infarction. The authors
stated that MI should be used when there is evidence of myocardial necrosis in a clinical setting consistent with
MI. Myocardial infarction was then classified by the clinical scenario into various subtypes. Type 1 is a
spontaneous MI related to ischemia from a primary coronary event (e.g., plaque rupture, thrombotic occlusion).
Type 2 is secondary to ischemia from a supply-and-demand mismatch. Type 3 is an MI resulting in sudden
cardiac death. Type 4a is an MI associated with percutaneous coronary intervention, and 4b is associated with instent thrombosis. Type 5 is an MI associated with coronary artery bypass surgery.3
A more common clinical diagnostic classification scheme is also based on electrocardiographic findings as a
means of distinguishing between two types of MI, one that is marked by ST elevation (STEMI) and one that is not
(NSTEMI). Management practice guidelines often distinguish between STEMI and non-STEMI, as do many of the
studies on which recommendations are based. The distinction between STEMI and NSTEMI also does not
distinguish a transmural from a nontransmural MI. The presence of Q waves or ST-segment elevation is
associated with higher early mortality and morbidity; however, the absence of these two findings does not confer
better long-term mortality and morbidity.4
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Prevalence and risk factors

Myocardial infarction is the leading cause of death in the United States and in most industrialized nations
throughout the world. Approximately 450, 000 people in the United States die from coronary disease per
year.5The survival rate for U.S. patients hospitalized with MI is approximately 95%. This represents a significant
improvement in survival and is related to improvements in emergency medical response and treatment
strategies.
The incidence of MI increases with age; however, the actual incidence is dependent on predisposing risk factors
for atherosclerosis. Approximately 50% of all MIs in the United States occur in people younger than 65 years.
However, in the future, as demographics shift and the mean age of the population increases, a larger percentage
of patients presenting with MI will be older than 65 years.
Six primary risk factors have been identified with the development of atherosclerotic coronary artery disease and
MI: hyperlipidemia, diabetes mellitus, hypertension, tobacco use, male gender, and family history of
atherosclerotic arterial disease. The presence of any risk factor is associated with doubling the relative risk of
developing atherosclerotic coronary artery disease.1

Hyperlipidemia
Elevated levels of total cholesterol, LDL, or triglycerides are associated with an increased risk of coronary
atherosclerosis and MI. Levels of HDL less than 40 mg/dL also portend an increased risk. A full summary of the
National Heart, Lung, and Blood Institute's cholesterol guidelines is available online.6

Diabetes Mellitus
Patients with diabetes have a substantially greater risk of atherosclerotic vascular disease in the heart as well as
in other vascular beds. Diabetes increases the risk of MI because it increases the rate of atherosclerotic
progression and adversely affects the lipid profile. This accelerated form of atherosclerosis occurs regardless of
whether a patient has insulin-dependent or noninsulin-dependent diabetes.

Hypertension
High blood pressure (BP) has consistently been associated with an increased risk of MI. This risk is associated
with systolic and diastolic hypertension. The control of hypertension with appropriate medication has been shown
to reduce the risk of MI significantly. A full summary of the National Heart, Lung, and Blood Institute's JNC 7
guidelines published in 2003 is available online.7

Tobacco Use
Certain components of tobacco and tobacco combustion gases are known to damage blood vessel walls. The
body's response to this type of injury elicits the formation of atherosclerosis and its progression, thereby
increasing the risk of MI. A small study in a group of volunteers showed that smoking acutely increases platelet
thrombus formation. This appears to target areas of high shear forces, such as stenotic vessels, independent of
aspirin use.8 The American Lung Association maintains a website with updates on the public health initiative to
reduce tobacco use and is a resource for smoking-cessation strategies for patients and health care providers.

Male Gender
The incidence of atherosclerotic vascular disease and MI is higher in men than women in all age groups. This
gender difference in MI, however, narrows with increasing age.

Family History
A family history of premature coronary disease increases an individual's risk of atherosclerosis and MI. The
cause of familial coronary events is multifactorial and includes other elements, such as genetic components and
acquired general health practices (e.g. smoking, high-fat diet).
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Pathophysiology and natural history

Most myocardial infarctions are caused by a disruption in the vascular endothelium associated with an unstable
atherosclerotic plaque that stimulates the formation of an intracoronary thrombus, which results in coronary artery
blood flow occlusion. If such an occlusion persists for more than 20 minutes, irreversible myocardial cell damage
and cell death will occur.

The development of atherosclerotic plaque occurs over a period of years to decades. The two primary
characteristics of the clinically symptomatic atherosclerotic plaque are a fibromuscular cap and an underlying
lipid-rich core. Plaque erosion can occur because of the actions of matrix metalloproteases and the release of
other collagenases and proteases in the plaque, which result in thinning of the overlying fibromuscular cap. The
action of proteases, in addition to hemodynamic forces applied to the arterial segment, can lead to a disruption of
the endothelium and fissuring or rupture of the fibromuscular cap. The loss of structural stability of a plaque often
occurs at the juncture of the fibromuscular cap and the vessel wall, a site otherwise known as the shoulder
region. Disruption of the endothelial surface can cause the formation of thrombus via platelet-mediated activation
of the coagulation cascade. If a thrombus is large enough to occlude coronary blood flow, an MI can result.
The death of myocardial cells first occurs in the area of myocardium most distal to the arterial blood supply: the
endocardium. As the duration of the occlusion increases, the area of myocardial cell death enlarges, extending
from the endocardium to the myocardium and ultimately to the epicardium. The area of myocardial cell death
then spreads laterally to areas of watershed or collateral perfusion. Generally, after a 6- to 8-hour period of
coronary occlusion, most of the distal myocardium has died. The extent of myocardial cell death defines the
magnitude of the MI. If blood flow can be restored to at-risk myocardium, more heart muscle can be saved from
irreversible damage or death.
The severity of an MI depends on three factors: the level of the occlusion in the coronary artery, the length of time
of the occlusion, and the presence or absence of collateral circulation. Generally, the more proximal the coronary
occlusion, the more extensive the amount of myocardium that will be at risk of necrosis. The larger the
myocardial infarction, the greater the chance of death because of a mechanical complication or pump failure. The
longer the period of vessel occlusion, the greater the chances of irreversible myocardial damage distal to the
occlusion.
STEMI is usually the result of complete coronary occlusion after plaque rupture. This arises most often from a
plaque that previously caused less than 50% occlusion of the lumen. NSTEMI is usually associated with greater
plaque burden without complete occlusion. This difference contributes to the increased early mortality seen in
STEMI and the eventual equalization of mortality between STEMI and NSTEMI after 1 year.
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Signs and symptoms

Acute MI can have unique manifestations in individual patients. The degree of symptoms ranges from none at all
to sudden cardiac death. An asymptomatic MI is not necessarily less severe than a symptomatic event, but
patients who experience asymptomatic MIs are more likely to be diabetic. Despite the diversity of manifesting
symptoms of MI, there are some characteristic symptoms.

Chest pain described as a pressure sensation, fullness, or squeezing in the midportion of the thorax

Radiation of chest pain into the jaw or teeth, shoulder, arm, and/or back

Associated dyspnea or shortness of breath

Associated epigastric discomfort with or without nausea and vomiting

Associated diaphoresis or sweating

Syncope or near syncope without other cause

Impairment of cognitive function without other cause

An MI can occur at any time of the day, but most appear to be clustered around the early hours of the morning or
are associated with demanding physical activity, or both. Approximately 50% of patients have some warning
symptoms (angina pectoris or an anginal equivalent) before the infarct.
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Diagnosis
Identifying a patient who is currently experiencing an MI can be straightforward, difficult, or somewhere in
between. A straightforward diagnosis of MI can usually be made in patients who have a number of atherosclerotic
risk factors along with the presence of symptoms consistent with a lack of blood flow to the heart. Patients who
suspect that they are having an MI usually present to an emergency department. Once a patient's clinical picture
raises a suspicion of MI, several confirmatory tests can be performed rapidly. These tests include
electrocardiography, blood testing, and echocardiography.

Diagnostic Procedures
The first diagnostic test is electrocardiography (ECG), which may demonstrate that a MI is in progress or has
already occurred. Interpretation of an ECG is beyond the scope of this chapter; however, one feature of the ECG
in a patient with an MI should be noted because it has a bearing on management. Practice guidelines on MI
management consider patients whose ECG does or does not show ST-segment elevation separately. As noted
earlier, the former is referred to as ST elevation MI (Fig. 1) and the latter as non-ST elevation MI (Fig. 2). In
addition to ST-segment elevation, 81% of electrocardiograms during STEMI demonstrate reciprocal ST-segment
depression as well.

Figure 1: Click to Enlarge

Laboratory Tests
Living myocardial cells contain enzymes and proteins (e.g., creatine kinase, troponin I and T, myoglobin)
associated with specialized cellular functions. When a myocardial cell dies, cellular membranes lose integrity, and
intracellular enzymes and proteins slowly leak into the blood stream. These enzymes and proteins can be
detected by a blood sample analysis. These values vary depending on the assay used in each laboratory. Given
the acuity of a STEMI and the need for urgent intervention, the laboratory tests are usually not available at the
time of diagnosis. Thus, good history taking and an ECG are used to initiate therapy in the appropriate situations.
The real value of biomarkers such as troponin lies in the diagnosis and prognosis of NSTEMI (Fig. 3).

Figure 2: Click to Enlarge

Imaging
An echocardiogram may be performed to compare areas of the left ventricle that are contracting normally with
those that are not. One of the earliest protective actions of myocardial cells used during limited blood flow is to
turn off the energy-requiring mechanism for contraction; this mechanism begins almost immediately after normal
blood flow is interrupted. The echocardiogram may be helpful in identifying which portion of the heart is affected
by an MI and which of the coronary arteries is most likely to be occluded. Unfortunately, the presence of wall
motion abnormalities on the echocardiogram may be the result of an acute MI or previous (old) MI or other
myopathic processes, limiting its overall diagnostic utility.

Figure 3: Click to Enlarge

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Treatment
The goals of therapy in acute MI are the expedient restoration of normal coronary blood flow and the maximum
salvage of functional myocardium. These goals can be met by a number of medical interventions and adjunctive
therapies. The primary obstacles to achieving these goals are the patient's failure to recognize MI symptoms
quickly and the delay in seeking medical attention. When patients present to a hospital, there are a variety of

interventions to achieve treatment goals. Time is muscle guides the management decisions in acute STEMI,
and an early invasive approach is the standard of care for acute NSTEMI.4

Medical Options
Antiplatelet Agents
The use of aspirin has been shown to reduce mortality from MI. Aspirin in a dose of 325 mg should be
administered immediately on recognition of MI signs and symptoms.4, 9 The nidus of an occlusive coronary
thrombus is the adhesion of a small collection of activated platelets at the site of intimal disruption in an unstable
atherosclerotic plaque. Aspirin irreversibly interferes with function of cyclooxygenase and inhibits the formation of
thromboxane A2. Within minutes, aspirin prevents additional platelet activation and interferes with platelet
adhesion and cohesion. This effect benefits all patients with acute coronary syndromes, including those with
amyocardial infarction. Aspirin alone has one of the greatest impacts on the reduction of MI mortality. Its
beneficial effect is observed early in therapy and persists for years with continued use. The long-term benefit is
sustained, even at doses as low as 75 mg/day.
The Clopidogrel and Metoprolol in Myocardial Infarction Trial/Second Chinese Cardiac Study (COMMIT-CCS 2)
trial evaluated the use of clopidogrel versus placebo in patients who were taking aspirin but not undergoing
reperfusion therapy. It demonstrated a benefit in favor of clopidogrel when used with aspirin.10 The Clopidogrel as
Adjunctive Reperfusion TherapyThrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) study compared
clopidogrel versus placebo in patients receiving fibrinolytics within 12 hours of STEMI and showed a benefit in
favor of clopidogrel as well.11 The current recommendations for antiplatelet agents is summarized inTable 1.

Table 1: Antiplatelet Medications

Treatment Modality

Aspirin

Clopidogrel

Medical

75-162 mg/day indefinitely

Optional: 75 mg/day 1

management
Bare Metal stent

month
162-325 mg/day 1 month, then 75-162 mg/day

300 mg loading dose,* then

indefinitely

75 mg/day 1 month

Sirolimus eluting

162-325 mg/day 3 months, then 75-162 mg/day

300 mg loading dose,* then

stent

indefinitely

75 mg/day 1 year

Paclitaxel eluting

162-325 mg/day 6 months, then 75-162 mg/day

300 mg loading dose,* then

stent

indefinitely

75 mg/day 1 year

(Cypher)

(Taxus)

* Note: No loading dose in patients older than 75 years.

Supplemental Oxygen
Oxygen should be administered to patients with symptoms or signs of pulmonary edema or with pulse oximetry
less than 90% saturation.4 The rationale for using oxygen is the assurance that erythrocytes will be saturated to
maximum carrying capacity. Because MI impairs the circulatory function of the heart, oxygen extraction by the
heart and by other tissues may be diminished. In some cases, elevated pulmonary capillary pressure and
pulmonary edema can decrease oxygen uptake as a result of impaired pulmonary alveolar-capillary diffusion.
Supplemental oxygen increases the driving gradient for oxygen uptake.1
Arterial blood that is at its maximum oxygen-carrying capacity can potentially deliver oxygen to myocardium in
jeopardy during an MI via collateral coronary circulation. The recommended duration of supplemental oxygen
administration in a MI is 2 to 6 hours, longer if congestive heart failure occurs or arterial oxygen saturation is less
than 90%. However, there are no published studies demonstrating that oxygen therapy reduces the mortality or
morbidity of an MI.

Nitrates
Intravenous nitrates should be administered to patients with MI and congestive heart failure, persistent ischemia,
hypertension, or large anterior wall MI.4, 9 The primary benefit of nitrates is derived from its vasodilator effect.
Nitrates are metabolized to nitric oxide in the vascular endothelium. Nitric oxide relaxes vascular smooth muscle
and dilates the blood vessel lumen. Vasodilatation reduces cardiac preload and afterload and decreases the
myocardial oxygen requirements needed for circulation at a fixed flow rate. Vasodilatation of the coronary arteries
improves blood flow through the partially obstructed vessels as well as through collateral vessels. Nitrates can
reverse the vasoconstriction associated with thrombosis and coronary occlusion.
When administered sublingually or intravenously, nitroglycerin has a rapid onset of action. Clinical trial data have
supported the initial use of nitroglycerin for up to 48 hours in MI. There is little evidence that nitroglycerin provides
substantive benefit as long-term post-MI therapy, except when severe pump dysfunction or residual ischemia is
present.4 Low BP, headache, and tachyphylaxis limit the use of nitroglycerin. Nitrate tolerance can be overcome
by increasing the dose or by providing a daily nitrate-free interval of 8 to 12 hours. Nitrates must be avoided in
patients who have taken a phosphodiesterase inhibitor within the previous 24 hours.4

Pain Control
Pain from MI is often intense and requires prompt and adequate analgesia. The agent of choice is morphine
sulfate, given initially IV at 5 to 15 minute intervals at typical doses of 2 to 4 mg.4 Reduction in myocardial
ischemia also serves to reduce pain, so oxygen therapy, nitrates, and beta blockers remain the mainstay of
therapy. Because morphine can mask ongoing ischemic symptoms, it should be reserved for patients being sent
for coronary angiography. This was downgraded to a IIa recommendation in the latest STEMI guidelines.

Beta Blockers
Beta blocker therapy is recommended within 12 hours of MI symptoms and is continued indefinitely.4, 9 Treatment
with a beta blocker decreases the incidence of ventricular arrhythmias, recurrent ischemia, reinfarction, and, if

given early enough, infarct size and short-term mortality. Beta blockade decreases the rate and force of
myocardial contraction and decreases overall myocardial oxygen demand. In the setting of reduced oxygen
supply in MI, the reduction in oxygen demand provided by beta blockade can minimize myocardial injury and
death (Table 2).

Table 2: Beta Blocker Therapy

Agent

Dosing

Original Trial

Metoprolol

15 mg IV 1 then 200 mg/day PO in divided doses

MIAMI19

Atenolol

5-10 mg IV 1, then 100 mg/day PO

ISIS-120

Carvedilol

6.25 mg bid titrated to 25 mg BID

CAPRICORN21

ISIS-1, International Studies of Infarct Survival-1; MIAMI, Metoprolol in Acute Myocardial Infarction.

The use of a beta blocker has a number of recognized adverse effects. The most serious are heart failure,
bradycardia, and bronchospasm. During the acute phase of an MI, beta blocker therapy may be initiated
intravenously; later, patients can switch to oral therapy for long-term treatment. The COMMIT-CCS 2 trial raised
safety concerns about the use of early intravenous beta blockers in high-risk patients.10 In some patients who are
considered high risk due to age or hemodynamic instability, it may be reasonable to hold off on early intravenous
therapy.
According to the 2007 guideline updates, anticoagulation should be added to standard medical therapy for most
patients after myocardial infarction.4

Unfractionated Heparin
Unfractionated heparin is beneficial until the inciting thrombotic cause (ruptured plaque) has completely resolved
or healed. Unfractionated heparin has been shown to be effective when administered intravenously or
subcutaneously according to specific guidelines. The minimum duration of heparin therapy after MI is generally
48 hours, but it may be longer, depending on the individual clinical scenario. Heparin has the added benefit of
preventing thrombus through a different mechanism than aspirin (Box 1).

Box 1: Unfractionated Heparin Dosing

Loading Dose

60 U/kg IV bolus
Max 5000 U if >65 kg or 4000 U if <65 kg

Maintenance Dose

12 U/kg/hr IV
Max 1000 U/hr if >65 kg or 800 U/hr if <65 kg

Titration Goal

PTT 50-70 sec

PTT, prothrombin time.

Low-Molecular-Weight Heparin
Low-molecular-weight heparin (LMWH) can be administered to MI patients who are not treated with fibrinolytic
therapy and who have no contraindications to heparin. The LMWH class of drugs includes several agents that
have distinctly different anticoagulant effects. LMWHs are proved to be effective for treating acute coronary
syndromes characterized by unstable angina and NSTEMI.4 Their fixed doses are easy to administer, and
laboratory testing to measure their therapeutic effect is usually not necessary (Table 3).

Table 3: Low-Molecular-Weight Heparin

Generic
name

Dalteparin

t1/2
(after SC

Dosing in ACS

FDA Approved Indications

120 U/kg SC bid

Prevention of ischemic complications in UA and

dosing)
3-5 hr

NSTEMI
Enoxaparin

4.5 hr

100 U/kg (1 mg/kg)

Prophylaxis of ischemic complications of UA and

SC q12h

NSTEMI when administered with aspirin

UA, unstable angina; NSTEMI, nonST segment elevation myocardial infarction.

Warfarin
Warfarin is not routinely used after MI, but it does have a role in selected clinical settings. The latest guidelines
recommend the use of warfarin for at least 3 months in patients with left ventricular aneurysm or thrombus, a left
ventricular ejection fraction less than 30%, or chronic atrial fibrillation.

Fibrinolytics
Restoration of coronary blood flow in MI patients can be accomplished pharmacologically with the use of a
fibrinolytic agent. Fibrinolytic therapy is indicated for patients who present with a STEMI within 12 hours of
symptom onset without a contraindication. Absolute contraindications to fibrinolytic therapy include history of
intracranial hemorrhage, ischemic stroke or closed head injury within the past 3 months, presence of an
intracranial malignancy, signs of an aortic dissection, or active bleeding. Fibrinolytic therapy is primarily used at
facilities without access to an experienced interventionalist within 90 minutes of presentation.9
As a class, the plasminogen activators have been shown to restore normal coronary blood flow in 50% to 60% of
STEMI patients. The successful use of fibrinolytic agents provides a definite survival benefit that is maintained for
years. The most critical variable in achieving successful fibrinolysis is time from symptom onset to drug
administration. A fibrinolytic is most effective within the first hour of symptom onset and when the door-to-needle
time is 30 minutes or less.9

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Angiotensin-converting enzyme (ACE) inhibitors should be used in all patients with a STEMI without
contraindications. ACE inhibitors are also recommended in patients with NSTEMI who have diabetes, heart
failure, hypertension, or an ejection fraction less than 40%. In such patients, an ACE inhibitor should be
administered within 24 hours of admission and continued indefinitely. Further evidence has shown that the benefit
of ACE inhibitor therapy can likely be extended to all patients with an MI and should be started before discharge.4,
9

Contraindications to ACE inhibitor use include hypotension and declining renal function. The most commonly

used ACE inhibitors are summarized in Table 4.

Table 4: ACE Inhibitors

Agent

Dosing (PO)

Original Trial

Captopri

6.25 mg tid titrated to 50 mg

SAVE: 3-16 days post-MI in asymptomatic patients with EF

tid

<40%22

Ramipril

1.25 mg bid titrated to 5 mg

AIRE: 3-10 days post-MI with symptoms of heart failure23

bid
Captopri

6.25 mg bid titrated to 50 mg

bid

Lisinopril

5 mg/day titrated to

ISIS-4: started within 24 hr of MI24

GISSI-3: started within 24 hr of MI25

10 mg/day

AIRE, Acute Infarction Ramipril Efficacy; EF, ejection fraction; GISSI-3, Gruppo Italiano per lo Studio della Sopravvivenza
nellInfarto Miocardico; ISIS-4, International Studies of Infarct Survival-1; MI, myocardial infarction; SAVE, Survival and
Ventricular Enlargemen.

ACE inhibitors decrease myocardial afterload through vasodilatation. One effective strategy for instituting an ACE
inhibitor is to start with a low-dose, short-acting agent and titrate the dose upward toward a stable target
maintenance dose at 24 to 48 hours after symptom onset. Once a stable maintenance dose has been achieved,
the short-acting agent can be continued or converted to an equivalent-dose long-acting agent to simplify dosing
and encourage patient compliance. For patients intolerant of ACE inhibitors, angiotensin receptor blocker (ARB)
therapy may be considered.

Glycoprotein IIb/IIIa Antagonists

Glycoprotein IIb/IIIa receptors on platelets bind to fibrinogen in the final common pathway of platelet aggregation.
Antagonists to glycoprotein IIb/IIIa receptors are potent inhibitors of platelet aggregation. The use of glycoprotein
IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) and in patients with MI and acute coronary
syndromes has been shown to reduce the composite end point of death, reinfarction, and the need to
revascularize the target lesion at follow-up. The current guidelines recommend the use of a IIb/IIIa inhibitor for
patients in whom PCI is planned. For high-risk patients with NSTEMI who do not undergo PCI, a IIb/IIIa inhibitor
may be used for 48 to 72 hours (Table 5).4

Table 5: Glycoprotein IIb/IIIa Inhibitors

Agent

Loading Dose (IV)

Abciximab

0.25 mg/kg

Maintenance Dose

Duration of

FDA Approved

(IV)

Infusion

Indications

0.125 g/kg/min

12-24 hr

Coronary intervention

Up to 72 hr

Acute coronary

max 10 g/min
Eptifibatid

180 g/kg

2 g/kg/min

syndrome
Coronary intervention

Tirofiban

0.4 g/kg/min for

30 min

0.1 g/kg/min

12-24 hr

Acute coronary
syndrome
Coronary intervention

Evidence is less well established for the direct thrombin inhibitor, bivalirudin. The 2007 American College of
Cardiology (ACC) and the American Heart Association (AHA) guidelines recommend bivalirudin as an alternative
to heparin therapy for patients who cannot receive heparin for a variety of reasons (e.g., heparin-induced
thrombocytopenia).4, 9

Statin Therapy
A statin should be started in all patients with a myocardial infarction without known intolerance or adverse
reaction prior to hospital discharge. Preferably, a statin would be started as soon as a patient is stabilized after
presentation. The Pravastatin or Atorvastatin Evaluation and InfectionThrombolysis in Myocardial Infarction 22

(PROVE IT-TIMI 22) trial suggested a benefit of starting patients on high-dose therapy from the start (e.g.,
atorvastatin 80 mg/day).12

Aldosterone Antagonists
In the Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, a
mortality benefit was seen with eplerenone administration in all post-MI patients, provided multiple criteria were
met. The criteria included concomitant use of an ACE inhibitor, ejection fraction less than 40%, symptomatic heart
failure or diabetes, a creatinine clearance greater than 30 mL/min, and a potassium level less than 5 mEq/dL.13 In
patients that meet these criteria, the use of eplerenone has a Class I indication.

Other Treatment Options

Percutaneous Coronary Intervention
Patients with STEMI or MI with new left bundle branch block should have PCI within 90 minutes of arrival at the
hospital if skilled cardiac catheterization services are available.9 Patients with NSTEMI and high-risk features
such as elevated cardiac enzymes, ST-segment depression, recurrent angina, hemodynamic instability,
sustained ventricular tachycardia, diabetes, prior PCI, or bypass surgery are recommended to undergo early PCI
(<48 hours). PCI consists of diagnostic angiography combined with angioplasty and, usually, stenting. It is well
established that emergency PCI is more effective than fibrinolytic therapy in centers in which PCI can be
performed by experienced personnel in a timely fashion.14 An operator is considered experienced with more than
75 interventional procedures per year. A well-equipped catheterization laboratory with experienced personnel
performs more than 200 interventional procedures per year and has surgical backup available. Centers that are
unable to provide such support should consider administering fibrinolytic therapy as their primary MI treatment.
Restoration of coronary blood flow in a MI can be accomplished mechanically by PCI. PCI can successfully
restore coronary blood flow in 90% to 95% of MI patients. Several studies have demonstrated that PCI has an
advantage over fibrinolysis with respect to short-term mortality, bleeding rates, and reinfarction rates. However,
the short-term mortality advantage is not durable, and PCI and fibrinolysis appear to yield similar survival rates
over the long term. PCI provides a definite survival advantage over fibrinolysis for MI patients who are in
cardiogenic shock. The use of stents with PCI for MI is superior to the use of PCI without stents, primarily
because stenting reduces the need for subsequent target vessel revascularization.15

Surgical Revascularization
Emergent or urgent coronary artery bypass grafting (CABG) is warranted in the setting of failed PCI in patients
with hemodynamic instability and coronary anatomy amenable to surgical grafting.9 Surgical revascularization is
also indicated in the setting of mechanical complications of MI, such as ventricular septal defect, free wall

rupture, or acute mitral regurgitation. Restoration of coronary blood flow with emergency CABG can limit
myocardial injury and cell death if performed within 2 or 3 hours of symptom onset. Emergency CABG carries a
higher risk of perioperative morbidity (bleeding and MI extension) and mortality than elective CABG. Elective
CABG improves survival in post-MI patients who have left main artery disease, three-vessel disease, or twovessel disease not amenable to PCI.

Implantable Cardiac Defibrillators

The results of a multicenter automatic defibrillator implantation trial have expanded the indications for automatic
implantable cardioverter-defibrillators (ICDs) in post-MI patients. The trial demonstrated a 31% relative risk
reduction in all-cause mortality with the prophylactic use of an ICD in post-MI patients with depressed ejection
fractions.16 The current guidelines recommend waiting 40 days after an MI to evaluate the need for ICD
implantation. ICD implantation is appropriate for patients in NYHA functional class II or III with an ejection fraction
less than 35%. For patients in NYHA functional class I, the ejection fraction should be less than 30% before
considering ICD placement. ICDs are not recommended while patients are in NYHA functional class IV.17

Treatment Outcomes
An individual patient's long-term outcome following an MI depends on numerous variables, some of which are not
modifiable from a clinical standpoint. However, patients can modify other variables by complying with prescribed
therapy and adopting lifestyle changes.

Stress Testing
Cardiac stress testing after MI has established value in risk stratification and assessment of functional
capacity.4 The timing of performing cardiac stress testing remains debatable. The degree of allowable physiologic
stress during testing depends on the length of time from MI presentation. Stress testing is not recommended
within several days after a myocardial infarction. Only submaximal stress tests should be performed in stable
patients 4 to 7 days after an MI. Symptom-limited stress tests are recommended 14 to 21 days after an MI.
Imaging modalities can be added to stress testing in patients whose electrocardiographic response to exercise is
inadequate to confidently assess for ischemia (e.g., complete left bundle branch block, paced rhythm, accessory
pathway, left ventricular hypertrophy, digitalis use, and resting ST-segment abnormalities).4
From a prognostic standpoint, an inability to exercise and exercise-induced ST-segment depression are
associated with higher cardiac morbidity and mortality compared with patients able to exercise and without STsegment depression.4 Exercise testing identifies patients with residual ischemia for additional efforts at
revascularization. Exercise testing also provides prognostic information and acts as a guide for post-MI exercise
prescription and cardiac rehabilitation.

Smoking Cessation
Smoking is a major risk factor for coronary artery disease and MI. For patients who have undergone an MI,
smoking cessation is essential to recovery, long-term health, and prevention of reinfarction. In one study, the risk

of recurrent MI decreased by 50% after 1 year of smoking cessation.18 All STEMI and NSTEMI patients with a
history of smoking should be advised to quit and offered smoking cessation resources, including nicotine
replacement therapy, pharmacologic therapy, and referral to behavioral counseling or support groups.4, 9 Smoking
cessation counselling should begin in the hospital, at discharge, and during follow-up. The American Lung
Association maintains a website (http://www.lungusa.org) with updates on public health initiatives to reduce
tobacco use; it is a resource for smoking cessation strategies for patients and health care providers. Other public
and private sources of smoking cessation information are available online as well.

Long-Term Medications
Most oral medications instituted in the hospital at the time of MI will be continued long term. Therapy with aspirin
and beta blockade is continued indefinitely in all patients. ACE inhibitors are continued indefinitely in patients with
congestive heart failure, left ventricular dysfunction, hypertension, or diabetes.4, 9 A lipid-lowering agent,
specifically a statin, in addition to diet modification, is continued indefinitely as well. Post-MI patients with
diabetes should have tight glycemic control according to earlier studies. The latest ACC/AHA guidelines
recommend a goal HbA1c of less than 7%.

Cardiac Rehabilitation
Cardiac rehabilitation provides a venue for continued education, reinforcement of lifestyle modification, and
adherence to a comprehensive prescription of therapies for recovery from MI including exercise training.
Participation in cardiac rehabilitation programs after MI is associated with decreases in subsequent cardiac
morbidity and mortality. Other benefits include improvements in quality of life, functional capacity, and social
support. However, only a minority of post-MI patients actually participate in formal cardiac rehabilitation programs
because of several factors, including lack of structured programs, physician referrals, low patient motivation,
noncompliance, and financial constraints.
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Summary

MI results from myocardial ischemia and cell death, most often because of an intra-arterial thrombus
superimposed on an ulcerated or unstable atherosclerotic plaque.

Despite advances in therapy, MI remains the leading cause of death in the United States.

MI risk factors include hyperlipidemia, diabetes, hypertension, male gender, and tobacco use.

Diagnosis is based on the clinical history, ECG, and blood test results, especially creatine
phosphokinase (CK), CK-MB fraction, and troponin I and T levels.

Outcome following an MI is determined by the infarct size and location, and by timely medical
intervention.

Aspirin, nitrates, and beta blockers are critically important early in the course of MI for all patients. For
those with STEMI and for those with new left bundle branch block, coronary angiography with
angioplasty and stenting should be undertaken within 90 minutes of arrival at facilities with expertise in
these procedures. Fibrinolytic therapy should be used in situations in which early angiographic
intervention is not possible.

Postdischarge management requires ongoing pharmacotherapy and lifestyle modification.

Back to Top

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